Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, gemcitabine, and
cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or
die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving fluorouracil together with
leucovorin, gemcitabine, and cisplatin works in treating patients with metastatic or
unresectable adenocarcinoma of the urothelium or urachal remnant (part of the bladder).

Study Design

5-FU continuous infusion over Days 1 - 5; Leucovorin once a day as a short infusion on Days 1 - 5; Cisplatin infusion over a few hours (usually 2-4 hours) once a day on Days 1 - 5; Gemcitabine infusion over 30 minutes on Days 1 & 5 only.

5-fluorouracil (5-fu)
5-FU

Day: 1 - 5 Dose: 200 mg/m2 IVCI daily x 5 days

leucovorin
Citrvorum

Day: 1 - 5 Dose:10 mg/m2 daily x 5 days

cisplatin
Platinol-AQ

Day: 1 - 5 Dose: 20 mg/m2 daily x 5 days

gemcitabine
Gemcitabine Hydrochloride

Day: 1 & 5 Dose: 200 mg/m2 (Two doses only)

Primary Outcomes

Measure

Number of Patients with Response

time frame:
Every 2 cycles (6 weeks)

Secondary Outcomes

Measure

Number of Patients with Dose-Limiting Toxicity

time frame:
Continous assessment during 21 day cycles

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria:
1. Histologic proof of cancer originating from the urinary tract with adenocarcinoma as
the predominant (>/= 50%) histology. Dr. Czerniak and/or Dr. Tamboli will be
consulted in equivocal cases of mixed histology. The Study Chairman is the final
arbiter in questions of mixed histology.
2. Bi-dimensionally measurable disease. All patients must have measurable or evaluable
disease. In general, liver and lung lesions should be at least 1 cm, and patients
with node-only disease should have lesions of >/= 1.5 cm in greatest dimension.
Patients with disease confined to bone may be eligible if a measurable lytic defect,
or soft-tissue component in present. Those without measurable disease may be eligible
if a serum marker is elevated (>/= 4 x ULN) (ie: CEA, CA-125, CA19-9, bhCG, etc).
3. (# 2 cont'd) The Study Chairman is the final arbiter in questions related to
measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on
bladder examination under anesthesia are considered to have measurable disease.
4. Patients are eligible if they have evidence of metastatic disease, or if their tumor
is surgically unresectable. In the absence of grossly metastatic disease, all
patients should be seen and evaluated by a member of the Urology staff to assess
their potential for resection.
5. Patients must have adequate physiologic reserves as evidenced by: • Life expectancy
of at least 9 months (based on co-morbidity) & at least 9 weeks based on the natural
history of their cancer. • Zubrod Performance Status (PS) of = 2; or 3 if of recent
onset and due entirely to the cancer and not to comorbidity, and especially if the
compromised performance status is due to uncontrolled pain which is expected to be
rapidly reversible when therapy starts.
6. (#5 cont'd) • Adequate bone marrow function as defined by absolute neutrophil count
>/= 1,800 and platelet count >/= 150,000. Supranormal values judged to be of benign
or inconsequential etiology are acceptable. • Transaminase (either SGPT or SGOT) =
2x the upper limit of normal. • Conjugated bilirubin = 2x the upper limit of
normal. • Creatinine clearance (either measured or estimated using the formula of
Cockcroft and Gault) of >/= 35 mL/min: CLcr = [(140-age) • wt(kg)]/[72 •Creat
(mg/dL)] (For females, x 0.85)
7. Patients must sign an informed consent indicating that they are aware of the
investigational nature of this study, in keeping with the policies of this hospital.
8. Patients must be at least 6 weeks out from pelvic irradiation, and must not have had
more than 10% of the bone marrow irradiated.
9. Patients with a history of cardiac disease, or evidence of ischemic heart disease on
EKG must have adequate cardiac function with an EF >/= 40% to participate.
10. Patient must be at least 18 years of age to participate in this study.
Exclusion Criteria:
1. Patients with metastases to the bladder from a primary adenocarcinoma arising outside
the urinary tract are ineligible.
2. Overt psychosis or mental disability or otherwise incompetent to give informed
consent.
3. A life threatening illness (unrelated to tumor) that would prevent completion of
protocol therapy.
4. Pregnant or nursing women, as the drug therapy regimen, and support medications pose
significant potential risks to the fetus and newborn.
5. Patients with second malignancies are eligible provided that the expected outcome
from the second cancer is such that this will not interfere in the delivery of this
therapy, or the assessment of response.
6. Patients with uncontrolled CNS metastases are not eligible.

Additional Information

Official title

Phase II Trial of 5-FU, Leucovorin, Gemcitabine, and Cisplatin for Adenocarcinomas of the Urothelial Tract and Urachal Remnant

Principal investigator

Arlene Siefker-Radtke, MD

Description

OBJECTIVES:
Primary
- Determine the response rate and overall survival of patients with metastatic or
unresectable adenocarcinoma of the urothelium or urachal remnant treated with
fluorouracil, leucovorin calcium, gemcitabine, and cisplatin.
Secondary
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients are stratified according to diagnosis (adenocarcinoma of the urothelium vs
adenocarcinoma of the urachal remnant).
Patients receive fluorouracil by vein (IV) continuously, leucovorin calcium IV once daily,
and cisplatin IV once daily on days 1-5 and gemcitabine IV on days 1 and 5. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3-6 months.
PROJECTED ACCRUAL: A total of 23-46 patients (7-18 with adenocarcinoma of the urachal
remnant and 16-28 with adenocarcinoma of the urothelium) will be accrued for this study.

Trial information was received from ClinicalTrials.gov and was last updated in December 2015.

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